New onset of palmoplantar keratosis triggered by COVID‐19 vaccination

Dear Editor,

Cutaneous manifestations have recently been reported as adverse events of the Coronavirus Disease 2019 (COVID)‐19 vaccines. ¹ , ² Of them, delayed large local reactions have been the most commonly reported cutaneous adverse events, followed by other heterogeneous common reactions such as urticarial eruptions, pernio, and pityriasis rosea‐like reactions, as well as new onset of autoimmune diseases, including flare‐ups of palmoplantar disease. ³ , ⁴

A 50‐year‐old Japanese man consulted our outpatient clinic with a 7‐month history of keratotic erythema on the bilateral soles and palms. He had received a first dose of vaccination for COVID‐19 (Pfizer‐BioNTech COVID‐19 vaccine) 6 days before the appearance of keratosis. He had received topical steroid and topical Chinese harp therapy (Shiun‐ko) without any improvement. On his initial visit, physical examination showed hyperkeratosis of bilateral soles (Figure 1A) and palms (Figure 1B). A biopsy specimen from the sole showed orthohyperkeratosis, hypergranulosis with interruption of the granular layer, irregular epidermal hyperplasia, vacuolar degeneration of the basal layer, and focal lichenoid lymphocytic infiltrate in the dermis (Figure 1C). Immunohistochemical staining of these lymphocytes was positive for IL‐17‐producing cells (Figure 1D), as well as high expression of IL‐17 receptor (R) on the keratinocytes in the stratum spinosum and the granular layer (Figure 1E). From the above findings, the diagnosis was palmoplantar keratosis triggered by COVID‐19 vaccination. Treatment included topical calcipotriol hydrate betamethasone dipropionate ointment and maxacalcitol ointment once a day, and his eruption gradually improved within 2 months.

FIGURE 1.

Hyperkeratosis on the bilateral soles (A) and palms (B). Biopsy specimen from the sole: orthohyperkeratosis, hypergranulosis, irregular epidermal hyperplasia, vacuolar degeneration of the basal layer, and focal lichenoid lymphocytic infiltrate in the dermis are seen (H&E staining) (C). Immunohistochemical staining for IL‐17 (D) and IL‐17R (E)

Vaccination for COVID‐19 has been widely given since 2022, and recent reports have suggested that the mRNA vaccine for COVID‐19 occasionally causes new onset or flares of autoimmune skin diseases such as psoriasis, lichen planus, bullous pemphigoid, and pemphigus vulgaris. ¹ , ² Moreover, the mRNA vaccine for COVID‐19 can cause flare‐ups of autoimmune disease, ⁵ as well as immune‐related adverse events in patients treated with immune checkpoint inhibitors, ⁶ both of which are related to IL‐17‐dependent pathways.

Conventional palmoplantar keratosis is known as a persistent thickening of the epidermis of the palms and soles, and it includes genetic, as well as acquired, conditions. ⁷ Its histological findings are nonspecific and consist of considerable hyperkeratosis, hypergranulosis, acanthosis, and sparse infiltration of lymphocytes in the upper dermis, ⁷ though the precise mechanisms remain unknown. On the other hand, recent reports suggested the contribution of IL‐17 to keratinocyte proliferation by directly activation of IL‐17–mediated cascade via the IL‐17R‐Act1‐TRAF4‐MEKK3‐ERK5 positive circuit. ⁸ , ⁹ Notably, IL‐17‐induced Steap4‐p63 expression forms a positive feedback loop through p63‐mediated TRAF4 expression, driving IL‐17‐dependent sustained activation of the TRAF4‐ERK5 axis for keratinocyte proliferation. ⁸ In our present case, IL‐17‐producing cells were detected in the area of focal lichenoid lymphocytic infiltrate in the dermis, and IL‐17R was highly expressed on the keratinocytes in the stratum spinosum and the granular layer of the epidermis in the present case. This report presents only a single case, but further cases may provide fundamental insights into the mechanisms of palmoplantar keratosis triggered by COVID‐19 vaccination.

AUTHOR CONTRIBUTIONS

Chisato Itabashi, and Taku Fujimura treated the patient and acquired the clinical data. Kentaro Ohuchi and Yuna Roh performed immunohistochemical staining. Chisato Itabashi and Taku Fujimura wrote the manuscript. Yoshihide Asano and Taku Fujimura supervised the study.

FUNDING INFORMATION

None.

CONFLICTS OF INTEREST

The authors have no conflicting interests to declare.

ETHICS STATEMENT

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The protocol for this human study was approved by the ethics committee of Tohoku University Graduate School of Medicine, Sendai, Japan (permit no. 2021–1‐1213).

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.